A detailed investigation of the topography of a new medullary ACTH/16K neuronal system is proposed, with a particular emphasis on the connectivity of this new system with brainstem regions subserving cardiovascular and autonomic homeostatis. These regions contain opiate receptors as well as opiocortin fibers, which have been assumed, until now, to emanate from the "bed nucleus" of opiocortin perikarya in the mediobasal hypothalamus (MBH). This assumption has fostered the belief that the profound modulatory effects of Beta-endorphn upon cardiovascular and autonomic homeostasis could be explained by the activation of these hypothalamic neurons and their fiber projections. The recent identification, in this laboratory, of a new group of neurons, immunoreactive with ACTH and 16K (POMC) antisera, located within the nucleus tractus solitarius (NTS) of the medulla, suggests that this hypothesis must be challenged. In the proposed studies, we will characterize the topography, connectivity and peptide content of this new ACTH/16K neuronal system using a variety of neuroanatomical and immunoassay techniques. Initially, we will define the topographic organization of these perikarya within the medulla, and investigate their immunoreactivity with a variety of antisera against different opiocortin peptides and fragments of the POMC molecule. Knife cuts of the arcuate neuronal system will be used to determine the extent to which the medullary cells distribute fibers to brainstem, cardiovascular and autonomic control centers. Combined HRP histochemical and immunocytochemical studies are proposed to address the neurons of origin of ACTH-ir terminal fields in brainstem. Using co-localization techniques we will identify the anatomical substrate for interactions (as best defined at the light microscope level) of this opiocortin system with neuropeptide and catecholamine systems thought to affect cardiovascular and autonomic functions. Finally, using microdissection and immunoassay technique in normal and deafferented animals, we will characterize the opiocortin peptide content of brainstem areas which contain the perikarya and fiber projections of this system.